Corticosteroid treatment in severe COVID-19 patients with acute respiratory distress syndrome

Abstract

BACKGROUNDCorticosteroids are widely used in patients with COVID 19, although their benefit-to-risk ratio remains controversial.METHODSPatients with severe COVID-19-related acute respiratory distress syndrome (ARDS) were included from December 29, 2019 to March 16, 2020 in 5 tertiary Chinese hospitals. Cox proportional hazards and competing risks analyses were conducted to analyze the impact of corticosteroids on mortality and SARS-CoV-2 RNA clearance, respectively. We performed a propensity score (PS) matching analysis to control confounding factors.RESULTSOf 774 eligible patients, 409 patients received corticosteroids, with a median time from hospitalization to starting corticosteroids of 1.0 day (IQR 0.0-3.0 days) . As compared with usual care, treatment with corticosteroids was associated with increased rate of myocardial (15.6% vs. 10.4%, P = 0.041) and liver injury (18.3% vs. 9.9%, P = 0.001), of shock (22.0% vs. 12.6%, P < 0.001), of need for mechanical ventilation (38.1% vs. 19.5%, P < 0.001), and increased rate of 28-day all-cause mortality (44.3% vs. 31.0%, P < 0.001). After PS matching, corticosteroid therapy was associated with 28-day mortality (adjusted HR 1.46, 95% CI 1.01-2.13, P = 0.045). High dose (>200 mg) and early initiation (≤3 days from hospitalization) of corticosteroid therapy were associated with a higher 28-day mortality rate. Corticosteroid use was also associated with a delay in SARS-CoV-2 coronavirus RNA clearance in the competing risk analysis (subhazard ratio 1.59, 95% CI 1.17-2.15, P = 0.003).CONCLUSIONAdministration of corticosteroids in severe COVID-19-related ARDS is associated with increased 28-day mortality and delayed SARS-CoV-2 coronavirus RNA clearance after adjustment for time-varying confounders.FUNDINGNone.

Keywords: COVID-19; Respiration.

Figure 1. Flow chart of the present study.

Figure 2. Survival curve during hospitalization according to corticosteroid therapy.

Kaplan-Meier survival curves before (A) and after propensity score matching (B).

Figure 3. Subgroup analysis of 28-day mortality according to corticosteroid treatment in the whole cohort.

APACHE II, acute physiology and chronic health evaluation II score; MV, mechanical ventilation; SOFA, sequential organ failure assessment.

Figure 4. Summaries of the balance of variables before and after propensity score matching.

SBP, systolic blood pressure; CKD, chronic kidney disease; CHD, chronic heart disease; CLD, chronic liver disease; COPD, chronic obstructive pulmonary disease; SMD, standard mean difference.

Figure 5. Cumulative incidence of SARS–CoV-2 RNA clearance according to corticosteroid therapy.

(A) Cumulative incidence of SARS–CoV-2 RNA clearance according to corticosteroid therapy by Kaplan-Meier plot. (B) Cumulative incidence of SARS–CoV-2 RNA clearance and 28-day mortality by competing risks analysis.